DESCRIPTION: The objective of this renewal proposal is to develop a practical chemical synthesis of camptothecin and to study the total synthesis of micrococcin P1 and of sulfur-containing prianosins and discorhabdins. It is reported that all these compounds are of interest as candidate antitumor agents, either because of their proven anticancer activity (camptothecin), or because of their cytotoxicity (discorhabdins and prianosins), or on accounts of their potent inhibition of protein synthesis (micrococcin). The principal investigator notes that development of new anticancer resources from the structural leads provided by his target compounds will be possible only through medicinal chemistry and SAR studies and that these endeavors, at least initially, require a synthetic avenue to the natural products. He indicates that whereas several syntheses of camptothecin have been recorded, the one proposed herein appears to be a particularly practical one and that no synthetic approaches to micrococcin or sulfur-containing discorhabdins/prianosins have yet been described. He finally notes that the research proposed herein will attempt to resolve such difficulties through the use of new chemical methodology developed in his laboratory.